Enhancing Antimicrobial Peptide Potency through Multivalent Presentation on Coiled-Coil Nanofibrils.

Area of Science:

• Biotechnology
• Materials Science
• Microbiology

Background:

• Antibiotic resistance poses a significant global health challenge.
• Novel delivery systems are crucial for enhancing antibiotic efficacy and overcoming resistance.
• Antimicrobial peptides (AMPs) show promise but often require improved delivery strategies.

Purpose of the Study:

• To develop a peptide-based scaffold (FF03) for multivalent presentation of antimicrobial peptides (AMPs).
• To evaluate the antimicrobial activity, safety, and mechanism of action of FF03-decorated AMPs.
• To establish a new platform for creating enhanced antimicrobial systems.

Main Methods:

• FF03, an α-helical coiled-coil peptide, was synthesized as a scaffold.
• The antimicrobial peptide IN4 was conjugated to the FF03 scaffold.
• Antimicrobial activity was tested against bacterial strains, including methicillin-resistant *Staphylococcus aureus* (MRSA).
• Nonhemolytic and noncytotoxic properties were assessed.
• Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and circular dichroism (CD) were employed.

Main Results:

• FF03 + IN4 fibrils demonstrated enhanced antimicrobial activity compared to unconjugated IN4 and standard antibiotics.
• The FF03 + IN4 system was nonhemolytic and noncytotoxic.
• SEM revealed that FF03 + IN4 nanofibers disrupt bacterial membranes, indicating a surface-level mechanism.
• TEM and CD confirmed that IN4 conjugation did not compromise FF03's fibril-forming properties or secondary structure.

Conclusions:

• The FF03 peptide scaffold enables efficient multivalent presentation of AMPs.
• FF03 + IN4 represents a safe and effective antimicrobial system with improved efficacy.
• This approach offers a promising strategy for developing next-generation antimicrobial agents against resistant bacteria.